Abundance of Maternal Mitochondrial Genome Is Dispensable up to the Mitochondrial Genome Activation in Post‐Implantation Embryos

Mitochondria in the egg are suggested to be crucial for the onset of new life. However, there is ambiguous knowledge about the necessity for fertilization and early embryonic development. Therefore, we created a conditional Tfam knockout (Tfam^loxP/loxP; Zp3-Cre) to produce Tfam^null oocytes for investigation of the mitochondrial abundance in oocytes and early embryos. This created mtDNA-depleted eggs, although the abundance of mitochondria did not change. Despite decreased mitochondrial membrane potential, Tfam^null oocytes matured and were fertilized, which led to embryo formation. These Tfam^null eggs were developed into mtDNA-deficient blastocysts. Both TFAM and mtDNA appear to be dispensable for the success of embryo implantation. Tfam expression and mtDNA replication rescue the mtDNA-deficient embryo after implantation, enabling passage through a post-implantation bottleneck, and allowing survivor embryos to develop into healthy individuals. Our findings highlight the uncoupled relationship between mtDNA replication and mitochondrial abundance in the growing oocyte and show the importance of the oocyte bulk mtDNA for successful mitochondrial activation in post-implantation embryos.